GI bleeding prevention in long term antiplatelet use.
GI bleeding prevention on long term antiplatelet use
I Dewa Nyoman Wibawa
Div.Gastroentero-hepatology,Dept.of Internal Medicine
Udayana Univ.;School of Medicine/Sanglah General Hospital.
Extended abstract
For the purpose of prevention of attacks or cardiovascular events later
often used antiplatelet either single or double. The use of antiplatelet to
prevent the occurrence of cardiovascular events is often accompanied by the
risk of gastrointestinal bleeding. Several approaches can be undertaken for
the purpose of preventing the occurrence of gastrointestinal bleeding in the
use of long-term antiplatelet therapy. One of the options is by using Proton
Pump Inhibitors (PPIs).
As we know that aspirin causes direct damage to the gastric epithelium
and inhibits prostaglandin production by the gastric mucosa, leading to
ulcerations and an estimated 2-fold increased risk of GI bleeding with lowdose aspirin alone.1,2 The additional use of antiplatelet and antithrombotic
agents with steroidal and no steroidal anti-inflammatory drugs increases the
risk.2,3
Use of PPIs in patients taking antiplatelet therapy has been associated
with a significant reduction in the risk of GI bleeding, ulcers, and erosions in
data from observational and randomized clinical trials.1
Pantoprazole and rabeprazole interfere minimally with the cytochrome
P450 system and may potentially not exhibit a similar interaction. 4,5 The use
of prasugrel instead of clopidogrel in acute coronary syndromes patients
undergoing percutaneous coronary intervention can be considered and has
been shown to cause platelet inhibition even in the face of clopidogrel no
responsiveness, albeit at the expense of increased bleeding.1
Newer antiplatelet agents that are not dependent on the cytochrome
P450 is enzymes such as ticagrelor could be used in acute coronary
syndromes treated invasively or conservatively. Administration of the PPI at a
different time than the administration of clopidogrel showed inconsistent
results in the studies that evaluated this strategy. It is unclear whether the
release pharmacokinetics of the particular omeprazole formulation used in
COGENT had any impact on the results of the trial. A different gastro
protective drugs such as H2 receptor antagonists can be used, although they
have been shown to confer a somewhat more modest protective effect than
PPIs.1
In patients with non-variceal upper gastrointestinal bleeding,
prophylaxis with anti-secretory drugs such as PPIs reduces the risk of GI
bleeding. Early endoscopy is useful for both the diagnosis and the therapeutic
management of GI bleeding. Antiplatelet therapy should be resumed
immediately after endoscopic hemostasis of GI bleeding, unless the bleeding
is life threatening.6
Based on the totality of evidence available to date, it does not support
a clinically significant impact of any pharmacokinetic or pharmacodynamics
interactions between PPIs and the current widely used antiplatelet agents.
Further evidence that will shed more light on this matter should come only
1
from randomized clinical trials because new retrospective studies, no matter
how statistically sound, will only add confusion to the matter. Until then, the
benefit of PPIs in reducing bleeding events (and treating GI symptoms) must
be factored into decision making when faced with patients with high GI
bleeding risk requiring antiplatelet therapy.1
Clinical characteristics can be used to guide the need for PPIs in
patients taking antiplatelet therapy (Figure 1).
Figure 1. Proposed algorithm for use of proton pump inhibitors (PPIs) in patients
requiring antiplatelet therapy. GI indicates gastrointestinal; NSAID, no steroidal antiinflammatory drug; and GERD, gastro esophageal reflux disease. 1
TABLE 1. Recommendations Available Related to GI Bleeding in Patients Taking
Anticoagulant and Antiplatelet Drugs.
A systematic review GI bleeding prevention on long term antiplatelet
use stated that gastroenterology guidelines tended to primarily focus on the
bleeding-associated risk for patient, and cardiovascular guidelines tended to
focus on the risk that is associated with discontinuing anticoagulant or
antiplatelet therapy. The specific recommendations of these are summarized
in Table 1. 7
A study of the effect of lansoprazole in preventing ulcer recurrence in
patients receiving long term low-dose aspirin was done. During a median
follow-up of 12 months, 9 of the 61 patients in the placebo group (14.8
2
percent), as compared with 1 of the 62 patients in the lansoprazole group (1.6
percent), had a recurrence of ulcer complications (adjusted hazard ratio, 9.6;
95 percent; confidence interval, 1.2 to 76.1). Of these 10 patients, 4 had
evidence of a recurrence of H. pylori infection and 2 had taken no steroidal
anti-inflammatory drugs before the onset of complications. Patients in the
lansoprazole group were significantly less likely to have a recurrence of ulcer
complications than patients in the placebo group (P=0.008). There was no
significant difference in mortality between the two groups. Base on this study
the author concluded that in patients who had ulcer complications related to
the long-term use of low-dose aspirin, treatment with lansoprazole in addition
to the eradication of H. pylori infection significantly reduced the rate of
recurrence of ulcer complications.8
Another study of lansoprazole for secondary prevention of gastric or
duodenal ulcers associated with long-term low-dose aspirin therapy was
completed. The risk of ulcer development was significantly (log-rank test,
P
I Dewa Nyoman Wibawa
Div.Gastroentero-hepatology,Dept.of Internal Medicine
Udayana Univ.;School of Medicine/Sanglah General Hospital.
Extended abstract
For the purpose of prevention of attacks or cardiovascular events later
often used antiplatelet either single or double. The use of antiplatelet to
prevent the occurrence of cardiovascular events is often accompanied by the
risk of gastrointestinal bleeding. Several approaches can be undertaken for
the purpose of preventing the occurrence of gastrointestinal bleeding in the
use of long-term antiplatelet therapy. One of the options is by using Proton
Pump Inhibitors (PPIs).
As we know that aspirin causes direct damage to the gastric epithelium
and inhibits prostaglandin production by the gastric mucosa, leading to
ulcerations and an estimated 2-fold increased risk of GI bleeding with lowdose aspirin alone.1,2 The additional use of antiplatelet and antithrombotic
agents with steroidal and no steroidal anti-inflammatory drugs increases the
risk.2,3
Use of PPIs in patients taking antiplatelet therapy has been associated
with a significant reduction in the risk of GI bleeding, ulcers, and erosions in
data from observational and randomized clinical trials.1
Pantoprazole and rabeprazole interfere minimally with the cytochrome
P450 system and may potentially not exhibit a similar interaction. 4,5 The use
of prasugrel instead of clopidogrel in acute coronary syndromes patients
undergoing percutaneous coronary intervention can be considered and has
been shown to cause platelet inhibition even in the face of clopidogrel no
responsiveness, albeit at the expense of increased bleeding.1
Newer antiplatelet agents that are not dependent on the cytochrome
P450 is enzymes such as ticagrelor could be used in acute coronary
syndromes treated invasively or conservatively. Administration of the PPI at a
different time than the administration of clopidogrel showed inconsistent
results in the studies that evaluated this strategy. It is unclear whether the
release pharmacokinetics of the particular omeprazole formulation used in
COGENT had any impact on the results of the trial. A different gastro
protective drugs such as H2 receptor antagonists can be used, although they
have been shown to confer a somewhat more modest protective effect than
PPIs.1
In patients with non-variceal upper gastrointestinal bleeding,
prophylaxis with anti-secretory drugs such as PPIs reduces the risk of GI
bleeding. Early endoscopy is useful for both the diagnosis and the therapeutic
management of GI bleeding. Antiplatelet therapy should be resumed
immediately after endoscopic hemostasis of GI bleeding, unless the bleeding
is life threatening.6
Based on the totality of evidence available to date, it does not support
a clinically significant impact of any pharmacokinetic or pharmacodynamics
interactions between PPIs and the current widely used antiplatelet agents.
Further evidence that will shed more light on this matter should come only
1
from randomized clinical trials because new retrospective studies, no matter
how statistically sound, will only add confusion to the matter. Until then, the
benefit of PPIs in reducing bleeding events (and treating GI symptoms) must
be factored into decision making when faced with patients with high GI
bleeding risk requiring antiplatelet therapy.1
Clinical characteristics can be used to guide the need for PPIs in
patients taking antiplatelet therapy (Figure 1).
Figure 1. Proposed algorithm for use of proton pump inhibitors (PPIs) in patients
requiring antiplatelet therapy. GI indicates gastrointestinal; NSAID, no steroidal antiinflammatory drug; and GERD, gastro esophageal reflux disease. 1
TABLE 1. Recommendations Available Related to GI Bleeding in Patients Taking
Anticoagulant and Antiplatelet Drugs.
A systematic review GI bleeding prevention on long term antiplatelet
use stated that gastroenterology guidelines tended to primarily focus on the
bleeding-associated risk for patient, and cardiovascular guidelines tended to
focus on the risk that is associated with discontinuing anticoagulant or
antiplatelet therapy. The specific recommendations of these are summarized
in Table 1. 7
A study of the effect of lansoprazole in preventing ulcer recurrence in
patients receiving long term low-dose aspirin was done. During a median
follow-up of 12 months, 9 of the 61 patients in the placebo group (14.8
2
percent), as compared with 1 of the 62 patients in the lansoprazole group (1.6
percent), had a recurrence of ulcer complications (adjusted hazard ratio, 9.6;
95 percent; confidence interval, 1.2 to 76.1). Of these 10 patients, 4 had
evidence of a recurrence of H. pylori infection and 2 had taken no steroidal
anti-inflammatory drugs before the onset of complications. Patients in the
lansoprazole group were significantly less likely to have a recurrence of ulcer
complications than patients in the placebo group (P=0.008). There was no
significant difference in mortality between the two groups. Base on this study
the author concluded that in patients who had ulcer complications related to
the long-term use of low-dose aspirin, treatment with lansoprazole in addition
to the eradication of H. pylori infection significantly reduced the rate of
recurrence of ulcer complications.8
Another study of lansoprazole for secondary prevention of gastric or
duodenal ulcers associated with long-term low-dose aspirin therapy was
completed. The risk of ulcer development was significantly (log-rank test,
P